Losartan Effects on Emphysema Progression Randomized Clinical Trial: Rationale, Design, Recruitment, and Retention.

The Losartan Effects on Emphysema Progression (LEEP) trial was designed to test the hypothesis that losartan slows progression of emphysema in COPD patients (NCT00720226). It was conducted by the Pulmonary Trials Cooperative consortium, in collaboration with the American Lung Association Airways Clinical Research Centers network. We describe the design of the trial and challenges for recruitment and follow-up of participants. LEEP is a placebo-controlled parallel randomized trial, allocation ratio of 1:1, with a planned sample size of 220. Primary eligibility criteria were mild emphysema based on high resolution computer tomography (HRCT) scans with 5 to 35% voxels <-950 Hounsfield Units (HU); airway obstruction based on spirometry; and not taking an angiotensin receptor blocker or angiotensin converting enzyme (ACE) inhibitor. Participants received either losartan or placebo for 48 weeks. 2,779 individuals were screened to enroll 220 eligible participants at 26 clinical sites, all located in the continental United States. Recruitment took 45% longer than planned (32 months vs. 22 months), with an average accrual rate of 6.7 participants per month. Recruitment challenges included identification of eligible participants who were not already taking or who did not have an established clinical indication for an angiotensin receptor blocker or ACE inhibitor drug and recalls of contaminated lots of losartan by the FDA. A number of recruitment initiatives were launched in response. Recruitment was completed in February 2020, just prior to nationwide shutdown of research activities due to the COVID-19 pandemic.